Assessing early changes in plasma HER2 levels is useful for predicting therapeutic response in advanced breast cancer: A multicenter, prospective, noninterventional clinical study

Background: Early prediction of treatment response is crucial for the optimal treatment of advanced breast cancer. We aimed to explore whether monitoring early changes in plasma human epidermal growth factor receptor 2 (HER2) levels using digital PCR (dPCR) could predict the treatment response in advanced breast cancer. Methods: This was a multicenter, prospective, noninterventional clinical study of patients with advanced breast cancer. All enrolled patients underwent blood testing to measure the HER2 levels by digital PCR before treatment initiation and once every 3 weeks during the study. The primary endpoints were^a the diagnostic value of dPCR for detecting HER2 status in the blood and^b the relevance of potential changes in the plasma HER2 level at 3 weeks from baseline for predicting treatment response. Results: Overall, 85 patients were enrolled between October 9, 2018, and January 23, 2020. dPCR had a specificity of 91.67% (95% CI: 80.61% to 97.43%) for detecting HER2 amplification, and the area under the receiver operating characteristic (ROC) curve was 0.84 (p < 0.01). A clinically relevant specificity threshold of approximately 90%, which was equivalent to a ≥15% decrease in the plasma HER2 ratio at 3 weeks from baseline, showed a positive predictive value of 97.37% (95% CI: 77.11% to 98.65%) in terms of predicting clinical benefit. Patients whose plasma HER2 ratio was reduced by ≥15% had a longer median progression-free survival (PFS) than those whose ratio was reduced by <15% (9.20 months vs. 4.50 months, p < 0.01). Conclusions: Early changes in the plasma HER2 ratio may predict the treatment response in patients with advanced breast cancer and could facilitate optimal treatment selection.